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Linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity

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Abstract

Linc-ROR is an oncogenic long non-coding RNA over-expressed in many kinds of cancer that promotes cancer cell proliferation. Arsenite is a determined carcinogen that increases the risk of skin cancer, but the carcinogenic mechanism of arsenite remains unclear. To explore whether and how linc-ROR plays a role in arsenite-induced carcinogenesis of skin cancer, we established arsenite-transformed keratinocyte HaCaT cells by exposing them to 1 μM arsenite for 50 passages. Then we examined the linc-ROR expression during the transformation and explored the effect of linc-ROR on the cell proliferation of arsenite-transformed HaCaT cells. We found that the linc-ROR level in HaCaT cells was gradually increased during arsenite-induced malignant transformation, and the activity of P53 was decreased, but the P53 expression was not significantly altered, indicating that linc-ROR may play a role in arsenite-induced HaCaT cell transformation that is associated with P53 activity but not P53 expression. We further demonstrated that linc-ROR down-regulation by siRNA significantly inhibited the cellular proliferation and restored P53 activity in arsenite-transformed HaCaT cells, suggesting that linc-ROR promotes proliferation of arsenite-transformed HaCaT cells by inhibiting P53 activity. Moreover, linc-ROR siRNA also down-regulated the PI3K/AKT pathway in arsenite-transformed HaCaT cells, and treatment with AKT inhibitor wortmannin restored P53 activity, implying that linc-ROR inhibits P53 activity by activating the PI3K/AKT pathway. Taken together, the present study shows that linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity through activating PI3K/AKT, providing a novel carcinogenic mechanism of arsenite-induced skin cancer.

Graphical abstract: Linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity

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Article information


Submitted
25 Mar 2020
Accepted
23 Apr 2020
First published
23 Apr 2020

Metallomics, 2020, Advance Article
Article type
Paper

Linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity

X. Li, C. Zuo, M. Wu and Z. Zhang, Metallomics, 2020, Advance Article , DOI: 10.1039/D0MT00076K

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